The aims of these studies are to understand (1) the role of cyclic AMP in the regulation of fatty acid and cholesterol synthesis and (2) the action of hormones and other factors on the formation of the peptide portion of lower density lipoproteins (d less than 1.035). Rat liver cells isolated by a collagenase-hyaluronidase digestion will be used to further delineate the decreased incorporation of labeled acetate into fatty acids and cholesterol produced by dibutyryl cyclic AMP. A comparison will be made between the inhibitory effects of dibutyryl cyclic AMP on cholesterol synthesis from acetate and mevalonate. Dose response curves will be obtained for the effects of epinephrine, glucagon and insulin on the incorporation of C14-acetate into cholesterol and fatty acids. We will examine factors responsible for the activation of fatty acid and cholesterol synthesis when a 10,000 x g supernatant from rat liver homogenates is preincubated at 37 degrees. Similar homogenates will be used to explore the mechanism and sites of inhibition of cholesterol and fatty acid synthesis by cyclic AMP. The effects of cyclic AMP will be tested on fatty acid synthesis in rat adipose tissue and on cholesterol synthesis in slices of small bowel from the rat and chicken. In isolated rat hepatocytes the incorporation of labeled leucine will be measured into lipoproteins released into the incubation medium and into apolipoproteins remaining within the cells. The relative incorporation of label into each of the apoproteins of VLDL will be determined. Regulation of lipoprotein synthesis will be studied by determining the effects of hormones and other factors on the synthesis and release of lipoproteins.